11-279434-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001276700.2(NLRP6):c.137C>T(p.Pro46Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000865 in 1,387,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

NLRP6
NM_001276700.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.98

Variant links:

Genes affected

NLRP6 (HGNC:22944): (NLR family pyrin domain containing 6) The protein encoded by this gene binds arginine-vasopressin and may be involved in the arginine-vasopressin-mediated regulation of renal salt-water balance. The encoded protein also mediates inflammatory responses in the colon to allow recovery from intestinal epithelial damage and protects against tumorigenesis and the development of colitis. Finally, this protein can increase activation of NF-kappa-B, activation of CASP1 through interaction with ASC, and cAMP accumulation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]

NLRP6 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055664062).

BP6

Variant 11-279434-C-T is Benign according to our data. Variant chr11-279434-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3200681.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRP6	NM_001276700.2 link	c.137C>T	p.Pro46Leu	missense_variant	Exon 2 of 8	ENST00000534750.6	NP_001263629.1	P59044-2
NLRP6	NM_138329.2 link	c.137C>T	p.Pro46Leu	missense_variant	Exon 2 of 8		NP_612202.2	P59044-1
NLRP6	XR_930848.2 link	n.300C>T		non_coding_transcript_exon_variant	Exon 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NLRP6	ENST00000534750.6 link	c.137C>T	p.Pro46Leu	missense_variant	Exon 2 of 8	2	NM_001276700.2	ENSP00000433617.1	P59044-2
NLRP6	ENST00000312165.5 link	c.137C>T	p.Pro46Leu	missense_variant	Exon 2 of 8	1		ENSP00000309767.4	P59044-1
NLRP6	ENST00000527946.1 link	n.376C>T		non_coding_transcript_exon_variant	Exon 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000891

AC:

AN:

1235214

Hom.:

Cov.:

AF XY:

0.00000499

AC XY:

AN XY:

600986

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000256

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000298

Gnomad4 OTH exome

AF:

0.0000197

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 12, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.50

DANN

Benign

0.93

DEOGEN2

Benign

0.066

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0065

LIST_S2

Benign

0.43

T;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.056

T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.1

D;D

REVEL

Benign

0.10

Sift

Benign

0.28

T;T

Sift4G

Benign

0.94

T;T

Polyphen

0.0

.;B

Vest4

0.075

MutPred

0.53

Gain of catalytic residue at P46 (P = 0.0097);Gain of catalytic residue at P46 (P = 0.0097);

MVP

0.014

ClinPred

0.061

GERP RS

-6.4

Varity_R

0.10

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over